The research is directed at identifying pharmacologic agents that will increase the tensile strength of vascular connective tissue. The proposal involves extensive drug testing of beta-adrenergic blockade combined with androgenic steroids for an effect on the tensile strength of the abdominal aorta of a domesticated inbred strain. The Broad Breasted White (BBW) turkey has a basic weakness of the abdominal aorta that leads to a relatively high incidence of spontaneous aortic dissecting aneurysms. We have identified certain androgenic steroids that when used in combination with beta-adrenergic blockade significantly increase the tensile strength measurements of the abdominal aorta from the BBW turkey. The possibility that the drugs increase the tensile properties of the abdominal aorta by altering collagen and elastin crosslinking is under investigation using: (a) the (3H) NaBH4-reduction technique; and (b) the rate of enzymic collagenolysis and elastolysis of collagen and elastin isolated from the abdominal aorta. In addition the possibility that the drugs alter the genome expression of collagen to produce a collagen type(s) with different intrinsic tensile properties is being tested. The ultimate objective is to test beta-adrenergic blockade in combination with selected androgenic steroids as a therapeutic regimen for patients with the Prolapsing Mitral Valve Syndrome, Cystic Medionecrosis of the Aorta, Dissecting Aortic Aneurysms and Hereditable Defects of Mesenchymal Tissue.